JPH06507892A - Cosmetic or pharmaceutical, especially dermatological, compositions containing Prunella extract - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] This invention essentially relates to cosmetic or pharmaceutical compositions containing Brunella extract, especially TECHNICAL FIELD The present invention relates to skin compositions.

More precisely, this invention provides a method for preventing or treating hair loss or alopecia areata. It has anti-inflammatory, anti-allergic, or anti-aging activity and promotes skin cell regeneration. For the preparation of promoting or conditioning cosmetic or pharmaceutical compositions, especially dermatological compositions. , an extract of Brunella or at least one Brunella (Prune IIa). ) Concerning the use of glycosides and cosmetic compositions for their application.

Plants of the genus Brunella, especially also known as common Prunella or fin prunella Prunella vulgar- isL,) or “saw grass” (“mlfoil”) is grown in temperate countries, especially It is a common labial flower (Labiatae) in Fras. Conventionally, this is a fresh tree. A liquid substance used in the form of a mouthwash, especially to treat sore throats and coughs. It's been coming.

It is also used as an infusion to treat bleeding and diseases of the gastrointestinal tract. It has been used. Antimutagenic activity of extracts of Prunella vulgaris el. However, more recently, Lee and Lin (Lee and Lin) 7 Yon Research (Mutation Research) J, No. 204, No. 2 29-234 (1,988).

The aging effect of the skin is particularly characterized by a slowing down of skin cell differentiation, resulting in As a result, slowing down the regeneration of cells, cell activity and cell morphology, and making the skin more radiant. Conversion of keratinocytes to corneocytes for a smooth, dry, wrinkled appearance This is known to slow down the conversion speed. Aging also has a negative effect on hair follicles. vinegar. The activity of hair follicle cells such as epidermal cells decreases due to the above effects, resulting in hair loss. Hair growth slows down and eventually the hair follicle degenerates and hair is completely lost.

Therefore, one of the main purposes of this invention is to provide hair with excellent effects on epidermal recovery. restores hair growth, prevents or slows hair loss, and improves the condition of the skin, hair and nails. Cosmetic or pharmaceutical compositions, especially for the skin, with good anti-aging effects The objective is to solve new technical problems that provide new formulations of compositions.

Another main object of the invention is to provide cosmetic or medicinal and/or Novel treatment of dermatological compositions with anti-inflammatory activity against erythema caused by external radiation radiation The aim is to solve novel technical problems that provide solutions.

Another main objective of this invention is to provide cosmetic or medical products with anti-allergic activity. elucidating novel technical problems that provide novel formulations of medicinal, especially dermatological compositions; It is.

Another main objective of the invention is to ensure the isolation of specific active substances or their synthesis. features that are unnecessary, satisfactory, and can be employed on an industrial scale. The purpose is to solve the above new technical problem in a simple way.

Thus, according to the first feature, the present invention provides a method for monitoring the regeneration and differentiation of keratinocytes. Brunella for preparing skin care, cosmetic or pharmaceutical, especially dermatological compositions. or at least one Brunella glycoside; can improve the functional status of the skin or maintain the good functional status of the skin, especially for dry skin. Ultraviolet irradiation is used to prevent or treat ichthyosis and to treat psoriasis. anti-inflammatory activity, or anti-allergic or anti-free radical activity. It has Cal activity.

In one particularly preferred embodiment, the above-mentioned Prunella is Prunella vulgaris . In other words, it is a normal Brunella.

In one particular embodiment, an extract of Brunella as described above or a composition of Prunella as described above. Glycosides can be extracted from the whole plant or specifically from the aerial parts of Brunella. can be obtained. Particularly preferably, these parts of the plant used are and dry it.

In particular, the above extract of Brunella may be obtained by the method indicated below. can be done, but is not limited to that. Dry substances, especially the aerial parts of Brunella Dry substances consisting of water, alcohols, preferably containing from 1 to 4 carbon atoms alcohols, chlorinated solvents, preferably having from 1 to 2 carbon atoms Consists of mixed solvents consisting of chlorinated solvents or mixtures of any of the above solvents Primary extraction is carried out using a solvent selected from the group.

Preferably, the primary extraction solvent is water, methanol, ethanol, methanol/water mixture. or an ethanol/water mixture.

The ratio of plant material to extractant is not necessarily critical and is generally 1:5 by weight. It is between 120 and 120.

The above primary extraction is carried out at a temperature between room temperature and the boiling point of the solvent used for extraction.

- Extraction is preferably carried out under human pressure with open reflux at 2 to 4 hours. In addition to this It is preferable to leave the mixture in an extraction solvent for 2 to 4 hours in the cold.

Once the extraction is complete, the solvent layer containing the extract is filtered and then concentrated and/or It is evaporated to dryness under reduced pressure "Y" to obtain the primary extract of Brunella of the present invention.

In one particular embodiment, the use of the invention relates to a mixture of Brunella glycosides. Ru. The mixture of Brunella glycosides according to the invention can be prepared in particular by the method described below. Obtained from the primary extract, concentrate and dry product of L of L. The above primary extract , low molecular weight ethers or ketones, especially ethers or isopropyl ethers, Acetone, or a non-polar material that is compatible with the primary extract, such as methyl ethyl ketone. into a neutral solvent and then stirred. The weight ratio of non-polar solvent is generally 1:1 for the primary extract. 5 to 100 parts. Any insoluble material or precipitate formed should be treated raw. contains a mixture of glycosides of the invention.

The mixture of glycosides obtained above may be produced by any method acceptable to those skilled in the art. It is preferable to

In particular, the above-mentioned insoluble substances and/or precipitates are redissolved in approximately 20 times their weight in water. do. The aqueous solution is then prepared using a slightly water-soluble aqueous solution such as water-saturated butanol. Extract 3-4 times with alcohol, for example using a 1:1 volume each time. alcohol layer are collected and evaporated under reduced pressure. Dissolve the residue in approximately 10 times the amount of water, then The solution is dialyzed against pure water for 4 to 5 days. The contents of the dialysis cell are cooled and vacuum dried. . The obtained glycoside mixture was purified by further dissolving the cooled vacuum-dried product in methanol, The solution can then be optionally refined by pouring it into ethyl ether.

Collect the resulting precipitate.

According to a second characteristic, the invention further provides anti-inflammatory or anti-allergic activity; is a cosmetic or cosmetic product with inhibitory activity against erythema caused by ultraviolet irradiation. or for pharmaceutical, especially dermatological, compositions, wherein the above-mentioned compounds are combined with active ingredients. and cosmetically or medicinally effective amounts of Prunella glycosides, if necessary. or in a pharmaceutically acceptable excipient.

In another embodiment, the invention provides a method for combating skin aging or improving skin function. Specially used as a protective barrier to improve skin conditions or maintain good functional status of the skin. For cosmetic or pharmaceutical, especially dermatological, compositions regulating the regeneration and differentiation of latin cells. The above composition is useful for cosmetic or pharmaceutical purposes as an active ingredient. amount of Brunella extract or one Prunella glycoside, if necessary, in cosmetics. or in a pharmaceutically acceptable excipient.

In yet another embodiment of the invention, the invention provides anti-free radical activity. The present invention relates to cosmetic or pharmaceutical, especially dermatological, compositions having the above-mentioned compositions. The composition contains as active ingredient a cosmetically or pharmaceutically effective amount of Brunella extract or contains one Prunella glycoside, if required, in a cosmetically or pharmaceutically acceptable manner. Contained in the formulation.

In another embodiment, the invention further prevents dry skin, especially ichthyosis. relating to cosmetic or pharmaceutical, especially dermatological, compositions for the treatment of The above composition contains a cosmetically or pharmaceutically effective amount of Brunella as the active ingredient. The extract or one Brunella glycoside can be used for cosmetic or pharmaceutical purposes if required. in an acceptable excipient.

The invention further relates to pharmaceutical compositions, particularly dermatological compositions for treating dislocations. The composition contains Brunella extract in a pharmaceutically effective amount as an active ingredient. extract or one Brunella glycoside, if necessary, with pharmaceutically acceptable excipients. Contains 6, In another preferred embodiment of the invention, the cosmetic or pharmaceutical composition of the invention The product, especially the dermatological composition, also contains xanthine, vitamins, especially vitamins A, B and El or derivatives thereof such as esters of vitamin A, tyrosine or Its derivatives such as glucose tyronate and malyltyrosine, quinine or Derivatives thereof, redness agents such as methyl nicotinate, literature European patent E P-A Kerati fibroblast culture suspension, as described in No. 272,920 Trace elements such as zinc, selenium, and copper, oxyacanthine (OXyBcanthine) or cephalanth bisbenzylisoquinoline alkaloids such as ine), progesterone, Cibrothyrone Acetate and Minoxidil' 5-α-reductase inhibitors such as azelaic acid and its derivatives, 1.4 -Methyl-4-athasteroids, especially 17-β-N,N-diethylcarhamoyl -4-methyl-4-aza-5-α-5-antrostan-3-one, or its and Serenoa repens extract. Contains a small effective concentration of one other active substance.

Particularly in the form of creams, milks, gels or lotions A cosmetic or pharmaceutical composition, in particular a dermatological composition, according to the invention comprises keratin. To regulate cell regeneration and differentiation, to counter the aging effects of skin conditions , prevent dry skin in order to improve the functional status of the skin and maintain a good functional status. or can be applied topically to treat dislocations. Wear.

According to this embodiment, the invention also improves the functional status of the skin and provides good functional status. to prevent or treat dry skin, or to treat dislocations. Treatment may include epidermal aging, inflammation, solar erythema, skin allergies, or skin irritation. It provides a method for treating diseases caused by the action of radicals, and the above-mentioned The method comprises administering at least one Brunella in an amount effective to produce the desired effect described above. extract or at least one Brunella glycoside for cosmetic or medical use if desired. Including incorporation into pharmaceutically acceptable excipients for topical application.

According to another embodiment, the invention also provides keratinocyte regeneration and differentiation. The present invention provides a method for producing cosmetic or pharmaceutical, especially dermatological, compositions. , this composition is used to treat dry skin in order to improve the functional status of the skin or maintain it in a good condition. Keratin microspheres, especially for the prevention or treatment of ichthyosis and for the treatment of dislocations. Anti-aging activity that regulates cell regeneration and differentiation, inflammation especially caused by UV irradiation have anti-inflammatory activity against, or anti-allergy or anti-free radical activity composition, and the process comprises at least one Brunella extract or and the composition is pharmaceutically or cosmetically acceptable. mixed with the resulting excipient, vehicle, or carrier.

In all embodiments, the concentration of Brunella extract or Brunella glycosides is A range of 0001% to 5% by weight in the composition is preferred.

The proportions stated in the description and claims are dry weight in the case of plant extracts. be.

In all embodiments, one particularly preferred embodiment of the invention Cosmetic or pharmaceutical compositions, especially dermatological compositions, according to the invention contain hydrated libidic It can also contain lamellar phases or lipisomes, which are the Brunnera extracts defined above. May or may not incorporate external materials.

The word “lipidic” in the expression “lipidic lamellar phase” is generally refers to all substances containing so-called aliphatic hydrocarbon chains containing 5 or more carbon atoms in Taste, this substance is usually called "fat".

According to the invention, lipidic lamellar phase or liposomal vesicles are formed. The lipids used for this purpose are amphiphilic lipids, that is, either ionic or nonionic It is a lipid consisting of molecules with hydrophilic groups and lipophilic groups, and these are compatible with each other. Depending on the amount of water in the mixture, lipids have a lipidic lamellar phase or a lipidic lamellar phase. can form ripisomal vesicles.

These lipids include, in particular, the following: diphospholipids, phosphoaminolipids glycolipids, polyoquinoethylenated aliphatic alcohols and optionally polymers. Reoxyethylated polyol esters. Such substances are e.g. or soybean lenotin, phosph-7teidylserine, sphingomyelin, cerebro glycolyl ceramide or oxyethylated polyglycerol stearate It consists of

According to the invention, at least one amphilipid lipid and cholesterol or is at least one hydrophobic lipid such as a sterol such as beta-nodosterol. It is preferable to use a mixed lipid consisting of The amount of hydrophobic compounds is expressed by weight. , generally should not exceed the amount of amphiphilic lipids, and preferably should not exceed half the amount of amphiphilic lipids. Must not be.

In one preferred embodiment, the Brunella extract or glycosides account for the total weight of the aqueous phase. of the hydrated libidic lamellar phase or liposomes at a concentration of 0001% to 5% of the amount introduced into the aqueous phase.

In yet another preferred embodiment, the Brunella extract or glycoside is Preferably from 0.01% to 30% by weight of the vidic phase, particularly preferably from 0.01% to 30% by weight of the vidic phase. at a concentration of from 0.0L to 10% by weight of the at least partially hydrated libide phase. Incorporated into the inoclamellar phase or the liposomal adhesive phase.

The expression "(I/at least partially incorporated") means that the substance is completely incorporated. Please note that this includes cases where this substance is incorporated and where certain amounts of this substance are incorporated. The glycosides or sapogenins or Prunella extract according to the present invention have hydrated libido. into the lamellar phase or into liposomes according to known production methods, e.g. Patent EP-Bl-0087993 = US Patent US-A-4 508 703 (also European patent EP-Bl-00101559 = US patent US- A-461 023).

In one embodiment of the above manufacturing method, the manufacturing method first comprises a hydrated lipidic lamina. comprising the addition of a phase or liposomes to a Brunella extract or Prunella glycosides; Brunella extract or Brunella glycosides are incorporated into the phase or into the liposomes. Second, the resulting mixture may or may not be incorporated. to a pharmaceutically or cosmetically acceptable excipient, vehicle or carrier. including.

Other objects, features and advantages of the invention will become apparent from the following illustrative description with reference to the examples. Let's be clear. The examples are provided merely as a means of illustration and thereby It is not intended to limit the scope of the invention in any way.

Percentages are expressed by weight in the examples unless otherwise stated. place for extracts In some cases, the amounts are expressed in terms of dry weight.

Dry 500g of Prunella vulgarisuel or ordinary Brunella in the air. Then, powder it and soak it in 1.2 L of methanol for about 2 hours. Mixture for 3 hours Reflux. After cooling, the solution is filtered through a N003 glass filter. the residue is the same Re-extract twice with IL methanol. Collect the filtrate three times and rotary evaporate Concentrate with a porator.

A methanol extract of Prunella according to the invention is thus obtained. if you need it , the above extract is heated at about 40°C to 60°C in a dryer until it reaches a constant weight. You can get a gift.

9 g of soy lecithin, 1 g of β-sitosterol and prepared according to Example 1 1 g of dried extract of Brunella in 100 ml of 9:1 chloroform/methanol mixture Dissolve in 1.

The solution follows the Bingham method, which is well known to industry technicians in the liposome field. Rotate until a film of lipid is deposited on the inner surface of the flask. Evaporate under reduced pressure in an evaporator at 60°C.

From the foam, add 89 g of distilled water to the flask. flask beam Stir until the lume is completely dispersed in the water at room temperature. It generally requires at least 2 to 4 hours of stirring is required. The dispersion was then heated to 150 watts using ultrasound. Homogenize for 10 minutes at 4°C.

The resulting liposomes have an average size of 1100n.

This suspension of liposomes was prepared separately in a conventional manner using 125% carbopolyte/ Mixed with l-940 (registered trademark) (Ca rbopo l 940CJ gel) 00g. It is preferable to gel them together. In this way, most of the above Prunella extract is combined. Approximately 200 g of a gel suspension of loaded liposomes is obtained. The concentration of this extract is 0.5% based on the total weight of the suspension.

Compositions containing different proportions of Brunella extract can be prepared by diluting them to different degrees. It can be seen that it is possible to provide a particularly effective method of formulation.

8. 50,000 pieces of altered human keratin in a 35mm diameter bowl. Cells were supplemented with covol% F-No-Nis (FC8 = fetal calf serum). , [-2, but no antibiotics were added to Gibco's N.E.M. MEM) inoculate into 2 ml.

Cultivation is carried out at 37°C for 24 hours.

After 24 hours of incubation, the medium was replaced with the same but test substance as shown below. Replace with w isomers containing different concentrations. The test was carried out three times, and the solvent of the test substance was A mold for comparison containing the sample was prepared and tested.

Cultivation is performed at 37° C. for 5 hours in an air atmosphere containing 5% carbon dioxide.

After 5 hours of incubation, cells were separated using Tribunone and placed in a Coulter-combiner. Count with known equipment.

The test substance is the crude methanol extract of Prunella vulgaris according to Example 1, D Dissolve in MSO.

This substance was added at a concentration ranging from 1 μg to 10 gg (dry extract) per ml of culture medium. A different II culture medium is placed in the culture medium.

The results obtained are shown in Table 1, and the results are shown in Table 1. The average number of cells is shown. The activity A of the test product is determined by the activity of the cells in each section of the dish. calculated from numbers According to statistical analysis, all differences between the number of cells in the test dish and comparator after incubation are significant. It was my intention.

Examples of Phospholipase A, (or PLA2) interference Phospholibase A2 during the production of allergy and inflammatory mediators, especially the inflammatory response of skin allergies The inhibitory activity of phosphatolylase A2 is contained in ・Of/<Iolo/Cal Chemistry (J, Bio　　　　　]Chem,) No. 102, pp. 147-154 (1987), H Dub I (Yu Cha Ng, I. Kuto, M. Tomita and K. Inouuni (H. WChang, 1 ．． Kudo, M. Tomita and K. Inoue) Measure according to the protocol.

-7,4 Suffuriverse A2 is isolated from the peritoneal fluid of Mentha nigra. huoshuo Reverse is a phosphatide radioactively labeled at carbon-14 at the 2-position of glycerol. Hydrolyze fatty acid ethanolamine: this releases fatty acids and The amount is measured in 2,000 L5-/yon of liquid. This M-element blocker prevents hydrolysis. decreases, and only a small amount of fatty acids can be detected.

In practice, Phospholibase A2 and the test extract were combined with 4mM Ca'' Place in 01 mol Tris buffer with pH=9, Incubate for 10 minutes at 7T. After this contact time, add labeled substrate and substrate Incubation is continued at 37°C for 40 minutes to allow hydrolysis of the cells. Then fat The fatty acids are extracted into the organic phase with n-heptane and counted by liquid/n-heptane.

Then the 50% inhibitor concentration (IC so) is determined.

50% interferent concentration for the methanol extract of Purufu according to Example 1. 17 gg ml was obtained, and this Brunella extract was converted to Phospholipase A2. This shows that 11LIE'Q has the first interfering activity.

7'/L not C) In the same test performed on aqueous extracts, the IC5° was 28 gg, / rnl Teatsuko No. 1 is Dunkin No. 1 with 41 females weighing between 400 and 450 g. - Tray (Dunkin Hart] ey) Kinnear big (guinea - pigs), six groups each consisting of six Guinea bigs. The animals were divided into groups of 1 and 5.

For one week before the start of the test, the animals were kept at a temperature of 20±1°C and humidity (hydrometry). )50±10% and exposed to light for IE312 hours. The day before the test, the animals were AESCULAPshave with 10mm comb r) Carefully shave the hair on the back, then use a brown razor to gently shave the hair on the sides. shave. Then I applied hair removal cream (approximately 2mm thick) and let it work for 15 minutes. .

Remove the cream with a wooden spatula, then rinse the guinea pigs with warm water and dry. .

Then, the same amount of irradiation was applied to both sides of the Guinea Big, and the irradiation area was 2cm2. do. The right side is coated with the test substance, which may be due to the test substance, and The test substance was added to the Spread over mm2. Apply Placebo on the left side.

The area treated with the test substance and the area not treated by applying Branbo on the left side. The effect of UV light on can be measured under the same conditions. Also, nothing about Planovo to observe the effect of the test substance and evaluate the area coated with the test substance in comparison with Plumbo. Can be done.

Test product is applied immediately after irradiation and every 2 hours up to 6 hours after irradiation.

I do not measure the amount of application, but spread it evenly (approximately 1 mg) over the entire area.

The irradiation device used is Biotronic UV312-365 (Biotroni c UV312-365) Mercury lamp (manufactured by Villeber Roumat) (Vi Albert-Loumat). Photocell that measures the intensity of ultraviolet light An ultraviolet energy measuring device consisting of is fixed to a support at the center of the irradiation area. child UVB (from Guinea pig) if the required energy m: The distance before the tap is 2Qcm) is set so that 2.16J/cm2- is programmed. Combine with shooting meter. The lamp switches automatically when it emits the full amount of energy can be cut.

This irradiation produces an erythema equal to 3±05 (see scale) in 6 hours.

Animals were given 0.5 ml/kg sodium bentoparbital 20 minutes before irradiation. Administer intramembranously to anesthetize.

After 6 hours of irradiation, macroscopically evaluate the erythema in each area according to the following criteria: 0. ...No erythema 1...Slight erythema but visible 2...Clearly Visible erythema 3...Substantial erythema After this complete evaluation, according to this indication, the Guinea pig with a score of 1 1 Guinea Pinog with a score of 2 and 1 Guinea Big with a score of 3. This is taken as a standard reference so that an intermediate score can be determined.

Guinea pigs that cannot be evaluated as either 1 (standard reference specimen) or 2 will be given a score of 1.5. evaluate.

The results are shown in Table ■.

The results of the difference (ultraviolet rays → - plumbo) - (ultraviolet rays + test substance) are shown in Table ■ (Continued) This is shown below.

The results obtained are used to calculate the percentage activity by the following formula: ＞＊＊＊　0.1 significant at % 2, the Prunella extract of this invention is an effective comparative example. It has an activity of 34.4% or 50% compared to domethanone's activity of 862%. I understand that.

The products of this invention thus exhibit excellent anti-inflammatory activity under experimental conditions, thereby , using products such as indomethacin, which previously were required to obtain satisfactory activity. There is no need to

The test extract according to the invention has a concentration of 0.2% by weight in the gel. Indomethacin is 1% concentration in hydroserine.

Many metamorphoses are observed in keratinocytes during the aging process. As the first one, Kera Chin cells do not develop uniformly throughout, but rather form a mosaic of cells. Ru. Although it is an unstructured term, the following distinction is made in the literature: a) Essential aging The stratum corneum becomes thicker, the stratum corneum becomes less sticky, and keratin becomes thicker. Metamorphosis of hyaline granules and cellular organelles is rarely seen either quantitatively or qualitatively. Not possible.

b) Aging due to chemical effects The intercellular spaces are enlarged, cytoplasmic vacuoles are present, and the tonofilaments are shorter and mesofilamentous. It has a Tsuyu-like distribution, various intercellular bridges have collapsed, and microvilli have decreased. .

For this study, skin samples were taken from the face of a 42-year-old woman during facial plastic surgery. obtained.

Cultures of keratinocytes isolated from this sample were placed in six Petri dishes in a conventional manner. Semi-qualified. Three of these are the methanol extract from Prunella in Example 1 with 0.25 µg/ml was administered and treated without cytotoxicity, and the other three cells were left untreated.

Those treated with Brunella extract of Example 1 and untreated (for comparison) Each cultured keratinocyte is embedded in resin. Then each cut A piece is prepared and observed using a transmission electron microscope. The results of this observation are shown in the table below. ■ In the case of the pull-free extract of this invention, highly differentiated cultures can be obtained, Tumor extract has very important anti-aging activity and its activity on keratinocyte differentiation. This indicates that the value should be adjusted.

Furthermore, due to the effect of normalizing the differentiation of keratinocytes, the composition of the present invention is particularly effective for normalizing the differentiation of keratinocytes. "normal" by maintaining its suppleness and functional role through protective layers. The epidermis of the skin can be maintained in good condition.

The composition of the invention may be used to prevent or treat dry skin, particularly ichthyosis. Can be done.

This invention can also be used to treat dislocations.

In fact, it should be pointed out that the phenomenon of dry skin and displacement is accompanied by abnormal keratinocyte differentiation. It is possible. In particular, keratinocytes that are displaced are undeveloped or immature. , the number and size of tonofilaments decrease, and some cells in the stratum corneum still remain Contains organs or even nuclei, indicating that differentiation is not proceeding correctly .

In the case of dry skin, especially in the case of ichthyosis, the differentiation of the keratin cell population is incomplete and the skin with malformations of latinohyaline grains and intercellular bridges. The epidermis exhibits abnormal keratinization , see the consequences of anomalies in barrier properties and loss of elasticity.

Tests have shown that the products of this invention are ey) Based on a study of the activity on the hair cycle of rats (all rats were 23 days old) It's on. The hair cycles of all rats are still in phase at this age.

More specifically, the aim is to prolong the hair growth phase, the so-called “developmental phase”. The purpose of this test is to demonstrate the effect of a test substance.

This is done as follows. At 24 days old, the hair of all rats has been thoroughly plucked. Shave on both sides of the lower back, leaving the hair as short as possible.

From age 25 to day 65 (the age of the rat), the dose was varied depending on the weight of the rat. and then give the test substance every 6 to 7 days. This dose is 0.5ml for day 25. Then, by the age of 65 days, it will be 2 ml.

For the first time from day 28, at regular intervals (approximately every 3 days), comb the hair. Remove it from the left side of the rat. 10 randomly selected hair roots from that tuft Observe under high magnification and see the characteristic shape of the roots. , count the number of hairs in a discernible developmental phase. Ru.

The percentage of hair in the developmental phase (growth phase) was determined for groups of 10 rats. determined as a function of time.

The study will consist of 30 rats divided into three groups of 10 each. The first group has the following composition ( Extract of Brunella according to example 1 giving the inventive preparation with composition "I")... ・・・・・・・・・0.1g-cephalanthine・・・・・・・・・・・・・・・ ...0.1g-propylene glycol 20. 0g - Distilled water 15.0 g-9 Sufficient amount of 5% ethyl alcohol...100.0g for the second group Give only the excipients listed below. The third group was the comparison group, which received no test substance! Uena stomach.

The results of this hair velocity study (trichogram as a function of time) are presented as average values. 7 and is represented in one accompanying figure.

This figure shows the percentage of hair in the developmental phase of a rat expressed on the ordinate and in days. The age of the child is shown on the abscissa.

The curve connecting the circles corresponds to the results obtained with the product according to the invention (composition "I-"). Correspondingly, the curve connecting the upward triangles is the one obtained by giving the excipient, and the curve connecting the downward triangles The curve connecting the corners is the one obtained in the comparative example, and the curve that does not give any product. It is.

In rats treated with the product according to the invention, especially in rats treated with vehicle alone. It can be seen that the developmental phase is longer than that of the previous model. This is especially true after Japan Ordinance 37. Significantly.

Thus, by prolonging the duration of the developmental phase, the Brunella extract of this invention Significantly slows down hair loss and promotes growth recovery.

Promote hair recovery growth and/or slow hair loss and/or epidermis various cosmetic or pharmaceutical compositions that promote or regulate the regeneration or growth of Examples are shown below.

0.2 g of Brunella extract obtained by water extraction by the same method as described in Example 1 Dissolve in 49.2 g of distilled water and pour this solution into Carpoball 940®. Gelification is effected by adding 50 g of 3% gel.

This gel can be given twice daily for a 4 month course of treatment.

Example 9 To prevent the disappearance of epidermis, especially on the scalp, prepare the following composition: Ru.

Brunella extract according to Example 1 01g-Panteno 0.1g - Keratin hydrolysis Agent・・・・・・・・・・・・・・・ 0.3g-Fragrance・・・・・・・・・・ ・・・・・・・・・・・・・・・ 0.1g - 40% alcohol Sufficient amount... ・・・・・・・・・100g Example 10 Styling gel to prevent hair loss by a method well known in the industry. Brunella extract according to Example 1 to prepare the following composition: ...0.2g - 150% gel of neutralized Carboball 940 (registered trademark)... 45 g = Phytantriol (registered trademark) 0.1 g(Phytantrio M - Remophor RH-40 (registered trademark) 0.5g (Cr emophor RH40 (! Cou protein/zinc complex compound... ・・・・・・　0.1g-Preservative・・・・・・・・・・・・・・・・・・・・・ ・・0.05 g - Aqueous excipient with perfume added Sufficient amount・・・・・・・・・・・・ Apply 100 g of the resulting gel to the area where the overlay disappears in the morning and evening for 6 months. .

Prepare the following composition.

Brunella extract according to Example 1 0.2 g Mofuore RH-40 (registered trademark) 0.5g - Fragrance... ・・・・・・・・・・・・・・・・・・ 0.1g-protein/zinc complex compound Item・・・・・・・・・・・・・・・ 0.05g-15% Carbopol 940 (Registered Trademark) Gel...45 g-Aqueous excipient Sufficient amount... ・・・・・・・・・・・・100g This gel is applied to the hair in the morning and evening for 6 months.

Composition A (heavily prepared) A cream containing 0.02% Prunella extract is prepared as follows. amount%) 1 Tefosse 1500 (registered trademark) 7.00 (Tef osse 150 (7') [Manufactured by Gattefosse] - Cetyl alcohol... ・・・・・・・・・・・・・・・ 2.0〇-Primor 352 (registered trademark)... ・・・・・・・・・25.00(Pr　imo　I　352’!’! [Made by Esso (ESSO)] Composition B (wt%) One theory: Inorganic water ・・・・・・・・・・・・・・・・・・ 54.40-Carbobo Rule 940 (registered trademark) 0.30 manufactured by Polyplastics Co., Ltd. (PolyplastiC)]-triethanolamine・・・・・・・・・・・・ ...0.30 Composition C (wt%) 1 Germaben ■ (registered trademark) 0,80 (Germ aben nM [Manufactured by Seppjc] Composition D (wt%) One theory is inorganic water... io, o.

- Prunella water extract (dry extract) 0.20 Composition A is 7 Heat to 5°C and then dissolve Carpobol 940® into the water of Composition B. Scatter. The gel is neutralized with triethanolamine. Solution B is heated to 75°C.

Composition A was prepared as an emulsicon in composition B at 75°C and then stirred while stirring. Cool to 40°C.

Then add composition C. Premix the ingredients of the composition and then add it to the formulation. Add. The product is homogenized and cooled to room temperature to obtain a cream.

This cream is applied twice daily in a 6-month treatment course to regenerate supple skin. Apply twice.

Example 13 Brunella extract according to Example 1 0.15g 1.5% Carpopol 980 (registered trademark) gel 48 g Sufficient amount of aqueous excipient ・・・・・・・・・・・・・・・・・・100 2182 times for 12 weeks Used.

Brunella extract according to Example 1 0.05g Hyalu Ronic acid・・・・・・・・・・・・・・・・・・ 1g glycerol・・・・ ・・・・・・・・・・・・・・・ 1g excipient for oil-in-water emulsion, sufficient amount ......100g Brunella extract according to Example 1... ...0.15g excipient for water-in-oil emulsion, sufficient amount...1 00g Use as a topical application to the scale area of the skin twice a day.

Of course, this invention includes all structural means technically equivalent to the described means, and including various combinations of In particular, this invention applies to cosmetic or pharmaceutical treatments of the skin. as well as cosmetic or pharmaceutical treatments of the integument, such as hair and nails. .

Continuation of front page (51) Int, C1,5 identification symbol Internal office reference number A 61 K 7/48 9051-4C (72) Inventor Dumas, Marta France 92700 Columbus, Ru de Landaustri map number I

Claims (1)

[Claims] 1. Improves the functional status of the skin or maintains the good functional status of the skin, and relieves dry skin characteristics. Intended for preventing or treating ichthyosis skin and treating psoriasis, Adjusts the regeneration and differentiation of latin cells and is anti-inflammatory against inflammation caused by ultraviolet irradiation. Cosmetic or antiallergenic activity, or antiallergic or antifree radical activity. or for preparing pharmaceutical, especially dermatological compositions, Prunella extract or less. How to use Prunella glycosides. 2. Please be sure that the above Prunella is Prunella vulgarisuel or ordinary Prunella. How to use request 1. 3. The above Prunella extract or the above Prunella glycosides are extracted from the whole plant. , or in particular obtained by extraction from the aerobic part of Prunella. 2 usage. 4. When the above extract of Prunella is mixed with water, alcohol, preferably 1 to 4 charcoal Alcohols containing elementary atoms, chlorinated solvents, preferably 1 to 2 carbon atoms chlorinated solvents, organic esters, preferably having from 3 to 6 carbon atoms. or a mixed solvent consisting of a mixture of any of the above solvents. The dry substance, preferably Prunella, is aerosolized using a solvent selected from the group consisting of Claims 1 to 3 obtained by carrying out a primary extraction of a dry substance consisting of Usage by one. 5. The above primary extraction solvent is water, methanol, ethanol, methanol/water mixture or ethanol/water mixture, chloroform and dichloromethane 5. Use according to claim 4, selected from the group, preferably water or methanol. 6. Use according to one of claims 1 to 5 relating to a mixture of Prunella glycosides. 7. The use according to claim 6, wherein the mixture of Prunella glycosides is obtained from the above-mentioned Prunella extract. Usage. 8. The concentration of Prunella extract or Prunella glycosides is 0.001 parts by weight in the total composition. 8. The use according to claims 1 to 7, wherein the amount is from 5% to 5% by weight. 9. concentration of xanthines, vitamins, especially vitamins A, B and E, or derivatives such as esters of vitamin A, tyrosine or its derivatives such as glucose Caustyrosinate and malyltyrosine, quinine or its derivatives, nicotine Redness agents such as methyl acid, protrusive fibroblast culture suspension, keratin hydrolyzate, Trace elements such as lead, selenium, and copper, oxyacanthin or cephalanthin Bisbenzylisoquinoline alkaloids such as progesterone, cyprote 5-alpha-reductase blockers such as Ron Acetate and Minoxidil® agents, azelaic acid and its derivatives, 1,4-methyl-4-azasteroids, especially 17-β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-α- selected from androstan-3-one or other selenoa repens extracts 9. The compound according to claim 1, comprising an effective concentration of at least one other active substance. How to use Totsu. 10. The composition also includes a hydrated lipidic lamellar phase or ribisomes, which may incorporate Prunella extract or Prunella glycosides as described above or Use according to one of claims 1 to 9, which is optional. 11. Anti-inflammatory or anti-allergic activity, or caused by ultraviolet irradiation It has inhibitory activity against erythema and is useful as an active ingredient for cosmetic or medicinal purposes. An effective amount of Prunella extract or at least one Prunella glycoside, if needed. cosmetic or pharmaceutical compositions in cosmetically or pharmaceutically acceptable excipients; products, especially skin compositions. 12. A cosmetically or pharmaceutically effective amount of Prunella extract or contains at least one Prunella glycoside, if required, for cosmetic or pharmaceutical use. contained in an excipient that can be used to combat skin aging or improve the functional status of the skin. The regeneration of keratinocytes as a particularly protective barrier to maintain a good functional status of the skin. Cosmetic or pharmaceutical compositions that regulate life and differentiation. 13. A cosmetically or pharmaceutically effective amount of Prunella extract or contains at least one Prunella glycoside, if required, for cosmetic or pharmaceutical use. cosmetic or pharmaceutical use in an acceptable excipient and having anti-free radical activity Compositions, especially dermatological compositions. 14. A cosmetically or pharmaceutically effective amount of Prunella extract or contains at least one Prunella glycoside, if required, for cosmetic or pharmaceutical use. for preventing or treating dry skin, especially ichthyosis. , cosmetic or pharmaceutical compositions, especially dermatological compositions. 15. As active ingredient, a pharmaceutically effective amount of Prunella extract or at least or one Prunella glycoside in a pharmaceutically acceptable excipient if necessary. , a pharmaceutical composition, especially a dermatological composition, for treating psoriasis. 16. The concentration of Prunella extract or Prunella glycosides is 0.001 parts by weight in the total composition. A composition according to one of claims 11 to 15, ranging from % to 5% by weight. 17. It also contains hydrated lipidic lamellar phases or lipisomes, which are described above. Optionally incorporates Prunella extract or at least one Prunella glycoside. 17. The composition of one of claims 11 to 16, which may or may not contain. 18, xanthine, vitamins, especially vitamins A, B and E, or their inducers. Conductors such as esters of vitamin A, tyrosine or its derivatives such as glucose Tyrosinate and malyltyrosine, quinine or its derivatives, methnicotinate redness agents such as gel, protrusive fibroblast culture suspension, keratin hydrolyzate, zinc, serum trace elements such as copper, oxyacanthine or cephalanthine. Unabisbenzylisoquinoline alkaloids, progesterone, cyproterone 5-α-reductase inhibitors, such as acetic acid and minoxidil®, gelaic acid and its derivatives, 1,4-methyl-4-azasteroids, especially 17 -β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-α-and rostan-3-one, or any other small amount selected from Serenoa repens extract. 18. The person of claim 11 to 17 comprising an effective concentration of at least one other active substance. composition. 19. Improve the functional status of the skin or maintain the good functional status of the skin, treat dry skin Particularly for preventing or treating ichthyotic skin and treating psoriasis, Regulates the regeneration and differentiation of keratinocytes, has anti-aging activity, anti-inflammatory activity, especially on UV irradiation. anti-inflammatory activity against inflammation caused by A method for producing cosmetic or pharmaceutical compositions, especially dermatological compositions, having radical activity. Yes, mixed with pharmaceutically or cosmetically acceptable excipients, vehicles or carriers. containing the use of Prunella extract or at least one Prunella glycoside Manufacturing method. 20. First, the Prunella extract or at least one Prunella glycoside is hydrated. adding the pidic lamellar phase or lipisomes and secondly the resulting mixture Adding products to pharmaceutically or cosmetically acceptable excipients, vehicles or carriers The manufacturing method according to claim 19, comprising: 21. In order to improve the functional status of the skin or maintain a good functional status of the skin, For preventing or treating dry skin or treating psoriasis, one Prunella extract or at least one Prunella glycoside, if desired. Incorporated into cosmetically or pharmaceutically acceptable excipients to achieve the desired effects mentioned above. skin aging, inflammation, solar erythema, Those who treat skin allergies or diseases caused by the action of free radicals Law.